Ulipristal acetate (UPA) is a progesterone receptor modulator which efficiently binds and inhibits progesterone receptor in progesterone target tissues.
UPA, formerly known as CDB-2914, designates 17□-acetoxy-11□-[4-N,N-dimethylamino-phenyl)-19-norpregna-4,9-diene-3,20-dione, represented by formula I:
UPA, and methods for its preparation, are described e.g., in U.S. Pat. Nos. 4,954,490; 5,073,548; and 5,929,262, as well as in international patent applications WO2004/065405 and WO2004/078709.
UPA has been approved for emergency contraception (under tradename EllaOne®), and for treatment of uterine fibroids (under tradename Esmya®). Various other potential clinical applications have been proposed in Chabbert-Buffet et al, Human Reproduction, 2005, 11(3): 293-307.
Other antiprogestins such as mifepristone and onapristone were developed for breast cancer treatment. Administration of mifepristone or onapristone in a second or third line of treatment, in 123 postmenopausal women with metastatic breast cancers induced objective response rate and disease stabilization in 11% and 43% of the patients, respectively (Romieu et al. 1987, Bull Cancer 74(4): 455-461; Klijn, et al. 1989, Cancer Res 49(11): 2851-2856). Unfortunately, clinical studies were not sustained because of the anti-glucocorticoid and liver toxic side effects of mifepristone and onapristone, respectively.
Long term UPA exposure may affect hormone-responsive tissues, and particularly breast tissue, as well. However, only gene reporter transactivation studies in T-47D breast cancer cell line were reported (Attardi et al. 2002, Mol Cell Endocrinol 188(1-2): 111-123; Attardi et al. 2004, J Steroid Biochem Mol Biol 88(3): 277-288). There is still a need for a therapeutic agent for treating, and even preventing breast tumors, while causing no or reduced side-effects.